Core C- Molecular Neurosciences / Viral Vectors The Molecular Neurosciences/Viral Vector Core will provide support and assist in the generation of viral vectors for use in the experiments proposed in Projects I-IV in this program project grant (PPG). The core will be part of the Cellular and Molecular Neurosciences Core Facility of the Hope Center for Neurological Disorders. The core has four major aims: 1) Assist Pi's with vector design, subcloning and virus production for experiments proposed in Projects I-IV; 2) Develop additional vector systems as needed, including viral vectors with expression targeted to specific cell types, such as neurons, astrocytes, oligodendrocytes and endothelial cells, 3) Validate gene silencing methodologies in the rodent brain, including lentiviral-mediated siRNA and expression of dominant negative proteins, and 4) Test new techniques for optimal viral delivery, including IV infusion for endothelial cell transduction. Lentiviral and adeno-associated viral vectors provide powerful tools for gene expression and gene silencing in the intact brain. The Molecular Neurosciences/Viral Vector Core will provide expertise and methods development that will expand the capabilities and resources of the individual investigators in Projects I-IV. RELEVANCE TO PUBLIC HEALTH: The Molecular Neurosciences/Viral Vector Core will enable Projects I- IV to further our understanding of mechanisms and potential therapies for cerebral ischemia. The viral vector systems used by the core, lentivirus and adeno-associated virus, are similar to viral systems currently used in clinical trials for human disorders, so viral therapies found to be efficacious in rodent models of stroke could potentially be translated into therapeutic agents for stroke.